Interactions of Npc1 and amyloid accumulation/deposition in the APP/PS1 mouse model of Alzheimer's

J Appl Genet. 2011 May;52(2):213-8. doi: 10.1007/s13353-010-0021-1. Epub 2010 Dec 18.

Abstract

Although Niemann-Pick C1 disease has frequently been called "juvenile Alzheimer's", the effects of introducing Npc1 mutations into a mouse model of Alzheimer's have not previously been performed. We have crossed Npc1 (+/-) mice with APP/PS1 "Alzheimer's" mice and studied Aβ42 accumulation and amyloid plaque formation. Mice heterozygous for Npc1 and positive for the APP and PS1 transgenes accumulated Aβ42 more rapidly than the APP/PS1 controls and this correlated, as expected, with the area of amyloid plaques. We conclude that the alterations of intracellular cholesterol present in Npc1 (+/-) mice can influence the progress of Alzheimer's disease in the APP/PS1 mouse model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Benzothiazoles
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Transgenic
  • Niemann-Pick C1 Protein
  • Niemann-Pick Diseases / genetics
  • Niemann-Pick Diseases / pathology
  • Peptide Fragments / metabolism
  • Plaque, Amyloid*
  • Proteins / genetics*
  • Regression Analysis
  • Thiazoles / metabolism

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Intracellular Signaling Peptides and Proteins
  • Niemann-Pick C1 Protein
  • Npc1 protein, mouse
  • Peptide Fragments
  • Proteins
  • Thiazoles
  • amyloid beta-protein (1-42)
  • thioflavin T